Rapid Test Apparatus

ABSTRACT

Provided herein are methods and devices for rapid testing of solid, semi-solid, or liquid specimens, such a stool, blood, urine, saliva, or swab specimens of the cervix, urethra, nostril, throat, and for environmental testing.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/625,813 filed Jan. 22, 2007, now allowed, which claims the benefit ofpriority to U.S. Provisional Application No. 60/761,580, filed Jan. 23,2006, each of which is incorporated by reference in their entirelyherein.

TECHNICAL FIELD

The invention is in general directed to methods and devices for rapidtesting of solid, semi-solid, or liquid specimens, such as stool, blood,urine, saliva, or swab specimens of the cervix, urethra, nostril, andthroat, and for rapid testing of environmental samples.

BACKGROUND

The testing of solid, semi-solid, or liquid specimens such as stool,blood, urine, saliva, or swab specimens of the cervix, urethra, nostril,or throat, as well as environmental specimens, such as food products,soil and dust, often requires pre-treating the specimens with a testbuffer, Pre-treating the specimens helps to dilute the specimen, extractsubstances to be detected from the specimen, or alter the specimen orsubstances. This pre-treatment results in a new sample solution that ismore suitable for the test substance to be detected. Typically, thecollected specimen is pre-mixed with the test buffer in a containerseparate from the test device used to detect the presence of aparticular test substance. In most testing protocols, a portion of theresulting sample solution is transferred to a second test location forreacting with a reagent to obtain a test result that indicates thepresence or quantity of the test substance in the specimen. For example,in a fecal occult blood test, a plastic tube is used to suspend thefecal specimen in a test buffer, which dissolves the blood components ofthe specimen. A breakable part of the plastic tube is then severed and aportion of the sample solution is released from the tube to a seconddevice, which is used to conduct an immunological hemoglobin test. Thetest result is read at a test area of the test device.

The procedures for severing the specimen treatment tube and transferringthe sample solution from the specimen treatment tube to the test devicecomplicates the test methods by requiring multiple steps. By requiringthat the sample be transferred, the work area may be contaminated due tosample leakage. Also, transferring the sample solution may lead toinaccurate results because of the possible transfer of inaccurate testvolumes. These methods are not convenient for onsite testing bynon-laboratory trained users. What is needed is a more simple, safe, andaccurate method of testing of solid, semi-solid, or liquid specimens.

SUMMARY

The present invention provides devices and methods for treating andtesting specimens that are simpler, safer to use, and more accurate. Incertain embodiments of the present invention are provided testassemblies that may be used for rapid testing of solid, semi-solid, orliquid specimens. In one non-limiting embodiment is provided a rapidtest device for testing the presence of fecal occult blood. In thisembodiment of the invention, feces sample collection, treatment, andtesting are performed all in one device. For example, a test buffer ispre-stored in the device in a sample receiving chamber, and at least onerapid lateral flow test strip for detecting hemoglobin is stored in aseparate test chamber, the test chamber. A sampling stick is attached tothe upper cap of the device for stool sample collection, and the fecesspecimen is transferred to the test buffer chamber using the samplingstick. The device is then shaken to distribute the feces sample into thebuffer, and the test is initiated by twisting a cap at the bottom of thedevice, allowing the sample solution to contact a lateral flow teststrip. The visual test result may then be read from the lateral flowtest strip within about 5 minutes.

In one embodiment is provided a test device comprising a test assembly,wherein the test assembly may be, for example, longitudinal, having anupper end, a lower end, a sample receiving chamber that has an openingat the upper end of the test assembly, a test chamber having an openingat the lower end of the test assembly and capable of receiving a reagentmember from the opening, a base capable of being coupled to the openingof the test chamber and sealing the lower end of the test assembly withthe reagent member inside the test chamber, and a means for liquidcommunication from the sample receiving chamber to the test chamber thatexists when the base is attached to the test assembly containing thereagent member inside the test chamber. The test assembly may be anyform having various appropriate dimensions for specimen collection andtesting, and may, for example, be in the form of a cup, or, for example,a tube. The testing devices of the present invention, for example, thetest assembly, may be of any suitable material, including, for example,plastic, such as, for example, a plastic selected from the groupconsisting of polyethylene, polypropylene, polystyrene, polyvinyl, andacrylonitrile butadiene styrene.

Also disclosed is a diagnostic testing device comprising a longitudinaltest assembly having an upper end, a lower end, a sample receivingchamber that has an opening at the upper end of the test assembly, atest chamber having an opening at the lower end of the test assembly andcapable of receiving a reagent member from the opening, a reagent memberinside the test chamber, a base coupled to the opening of the testchamber, wherein the base seals the lower end of the test assembly withthe reagent member inside the test chamber, and a means for liquidcommunication from the sample receiving chamber to the test chamber.

The method for using the test assembly to make a diagnostic testingdevice comprises introducing a reagent member capable of reacting withan assay sample and producing a signal indicating the presence orquantity of an analyte of the assay sample into the test chamber fromthe lower end of the test assembly and attaching the base to the lowerend of the test chamber.

The method for using a testing device of the invention comprisesintroducing a sample solution into the sample receiving chamber,activating the sample communication means from the sample receivingchamber to the test chamber and reading the test result of the reagentmember.

The test device of the invention may be used, for example, for testinganalytes selected from a group of analytes consisting of but not limitedto drugs of abuse, hormones, tumor markers, cardiac markers, infectiouspathogens, and environmental pollutants. The test sample solution is asolution, which is suspected of containing certain levels of theanalyte. Such sample solution is selected from a group of solutionsincluding body fluids including urine, saliva, plasma or serum, blood,and spinal fluid. The sample solution may also contain a treatmentsolution, such as water, pH or protein buffer. For example, dust orpowders suspected of containing drugs, explosives, or infectioussubstances may be dissolved in water or a pH buffer solution fortesting, using a device of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of a device of the invention.

FIG. 2 is an exploded view of the same device of FIG. 1

FIG. 3 is a top view of a test assembly of the invention.

FIG. 4 is a bottom view of the same part of FIG. 3.

FIG. 5 is an elevated perspective view of another device of theinvention.

FIG. 6 is an exploded view of the same device of FIG. 5.

FIG. 7 is an elevated perspective view of the sample device of FIG. 5 ina test position.

FIG. 8 is a perspective view of a device of the invention.

FIG. 9 is an exploded view of the same device of FIG. 8.

DETAILED DESCRIPTION

FIG. 1, in conjunction with FIG. 2 through FIG. 4, depicts a device ofthe invention. The sample collection and testing device comprises atesting assembly 110 and a base 120.

The test assembly 110 is longitudinal having wall 111, upper end 112,lower end 113, and septum wall 114 separating the interior of the testassembly into two chambers, a sample receiving chamber 115, and testchamber 116. The septum wall has a bottom section 117 that bends awayfrom the exterior wall 111 and a top section 118 that connects to theexterior wall 111. The bottom section 117 of the septum wall comprises ahole 119, a bottom opening of the sample receiving chamber. The exteriorwall has thread 109 on the interior side at the bottom end.

The base 120 comprises a handle section 121, insert section 122 havingthread 123 and plug 125 for sealing off the bottom opening of the samplereceiving chamber. Rubber o-ring 124 around the insert section 122serves as a sealant.

In this embodiment, The reagent member 140 comprises a wick section 141and a test area 142 comprising an assay reagent 143. When a samplesolution contacts the wick section of the reagent member, the samplesolution wicks up the wick section to the test area and reacts with thereagent. As a result, the presence or quantity of the test substance inthe sample solution is detected.

A rubber o-ring 126 is provided as a sealant that closes the hole 119.

Optional cap 130 comprises handle 131, and sampler pin 132.

With an assay reagent member 140 inserted in the test chamber 116, thebase is capable of tightly fitting to the bottom end of the testassembly, sealing off the bottom end of the test assembly, with the plug125 and the o-ring 126 capable of sealing off the bottom opening of thesample receiving chamber;

When a sample solution is introduced into the sample receiving chamber,loosening the base 120 opens up the plug 125 and the o-ring 126 from thehole 119 and allows the sample solution to flow through the hole 119 andcontact the reagent member 140 of the test chamber 116. The assay resultof the sample solution, on the assay reagent member 140, can be readthrough the wall 111 at the test chamber section.

There are several options for this device to adapt to specific needs.First, with the reagent member inserted inside the test chamber, thebase fitting into the bottom end of the test assembly with the plug 125sealing off the bottom opening of the sample receiving chamber, a samplesolution can be kept inside, or stored, inside the sample receivingchamber for future testing. Thus, a sample solution may be prepared, andthe test conducted at a later time. For example, a patient may obtain asample and the device may then be given to a laboratory technician, orother trained personnel for conducting he test and interpreting theresults. Alternatively, a buffer solution for treating or diluting atest sample can be kept inside the sample receiving chamber before thesample is introduced into the sample receiving chamber. Secondly, theplug 125 or o-ring of the base 120 can be omitted from the device or thebase be kept loose so that the passage between the sample receivingchamber and the test chamber is kept open. When a sample solution isintroduced into the sample receiving chamber, a volume of the samplesolution automatically flows from the sample receiving chamber into thetest chamber through the sample passage or hole at the bottom section ofthe test assembly.

The optional cap 130 seals off the top opening of the sample receivingchamber. Its optional sampler pin is capable of collecting liquid ornon-liquid samples and introducing the sample into the sample receivingchamber. Liquid samples include, for example, but are not limited to,blood, urine, saliva, water, mucus, or other fluid samples. Non-liquidsamples include, for example, powder, stool, dirt, dust, and other dryor semi-dry samples.

Other means for permitting liquid communication from thesample-receiving chamber to the test chamber may be employed in thedevice. For example, simple modification to the device of FIG. 1 is, inone embodiment, a test assembly of the invention wherein the hole 119 issealed or plugged, comprising a pin or other sharp edge or protrusionconnected to the top surface of the base that is capable of breaking theseal or removing the plug when the base is turned or pushed against thetest assembly. In this embodiment, the sample solution flows through thehole once the seat is broken or plug is removed, or, in anotherembodiment, the solution flows through the hole after the seal is brokenof plug removed. In this embodiment, in one example, the hole is sealedwhen the cap is loosely fitted, and is unsealed when the cap istightened, breaking the seal with the pin.

FIG. 5, in conjunction with FIG. 6 and FIG. 7, depicts anotherembodiment of the present invention. Device 200 comprises a testassembly 201 comprising an upper end 202 and a lower end 203, a samplereceiving chamber 204 comprising a test buffer 205 and a test chamber206 comprising a reagent member 207. A bottom part 208 closes the lowerend of the test assembly 201, a cap 209 closes the upper end of the testassembly, and a means, such as a pincap 210 is provided for enablingliquid flow from the sample receiving chamber 204 to the test chamber206. The test assembly 201 comprises a plastic tube structure comprisinga tubular interior wall 211 and exterior wall 212 that join together atthe neck area 227. The double layer sidewall forms an interior samplereceiving chamber 204 and a test chamber 206. A breakable seal 213 sealsoff the lower end opening of the interior wall 211. The bottom part 208sized to fit the lower end of the test assembly seals off the testassembly 206 from the lower end. The bottom part 208 comprises an upperend 214 and lower end 215, a sidewall 216 for fitting to the interior ofthe lower end of the test assembly, and a through hole 217 sealed off bya breakable seal 218 at the upper end 214. The pincap 210 comprises arod 219 sized to fit into the through hole 217 of the bottom part andcapable of breaking the breakable seals 218 and 213 when forced into thethrough hole from the lower end of the through hole. The cap 209comprises a handle section 220 and an insert section 221 sized to fit tothe upper opening 202 of the test assembly and closes the upper end ofthe assembly.

The reagent member 207 comprises an upper end 222 and lower end 223, atest area 224 proximal to the upper end 222 and a wick section 225proximal to the lower end 223. The test area comprises at least onereagent 226. A liquid in contact with the wick section 225 is capable ofwicking through the wick section to the test area 224 and contacting thereagent 226. The reagent member is disposed inside the test chamber withthe upper end oriented towards the upper end of the test assembly andwith the lower end of the reagent member oriented to the lower end ofthe test assembly.

The breakable seals of the test assembly are a hydrophobic barrierselected from a group consisting of plastic, rubber, and foil, attachedto the sidewall of the sample receiving chamber. The seal breaking meansfor breaking the breakable seal includes any means capable ofpenetrating, tearing, or removing a portion of the breakable seal whenthe device is in a test position. In an embodiment of the invention, theseal breaking means is a stick inserted from the upper end of the samplereceiving chamber capable of breaking the seal. The stick, in exemplaryembodiments, is designed to be sanitary, that is, to not contaminate thespecimen or sample solution. In another embodiment of the invention, theseal breaking means is a structure attached to the test module containercapable of breaking the seal from the lower end of the sample receivingchamber.

FIG. 8, in conjunction with FIG. 9, depicts a device of anotherembodiment of the invention. The device 300 comprises an assembly 310comprising a cup shaped transparent part 311 having an exterior wall orside wall 312, upper opening 313, lower opening 314, and a septum 315.The septum 315 is connected to the side wall 312 and separates the cupinterior into an upper section 316 and a lower section 317 connectedthrough a through-hole 318. A septum comprises a section 319 that is atan angle with the side wall and another section 320 that bends upward toform a pocket 321, a reagent member receptacle, with the side wall. Thereagent member receptacle 321 contains a reagent member, an absorbenttest strip comprising a wick section 331, a test area 332 comprising areagent 333. A bottom part 340 is sized to fit to the lower opening ofthe cup part with the reagent member inside the reagent memberreceptacle. A vent hole 341 is a through hole of the bottom part 340. Aporous plug 342 that is air permeable and sample solution impermeablefills in the through hole 341. An optional cap 350 is sized properly tofit to the upper opening 311

The porous plug comprises a porous material of the desired property—airpermeable and sample solution impermeable. Those of ordinary skill inthe art are familiar with materials that may be used to form the porousplastic plug, such as, for example, but not limited to, polyethylene andpolytetrafluoroethylene. The median pore size in the porous plastic plugmay range from 3 microns to an upper limit which is dependent on thehydrophobicity of the plug material. Air and liquid permeability ofporous plugs is related to the pore size and the surface property of theporous material. To achieve the desired property, the pore size of theplug is generally smaller than 30 microns, for example, 10-20 microns.Coating the surface of the porous material with a layer that will meltand forms a gel upon contact with the sample solution is another way toachieve the desired property. Such gel forming material can be selectedfrom a group consisting gum, gelatin, long change polysaccharides, andproteins.

The reagent member may comprise more than one test reagent for detectingmore than one test substance in the sample solution. For example, thedevice 300 may contain more than one absorbent test strip each fordetecting a different test substance, such as a drug of abuse. When asample solution, such as a urine specimen, is introduced into the devicefrom the upper opening, the samples flows to the lower section of thedevice and reacts with the reagents. Therefore, multiple testsubstances, such as drugs of abuse, can be detected simultaneously. Whenthe liquid level in the lower section of the device reaches the porousplug, the air vent through the plug closes. Additional liquid flow fromthe upper section to the lower section stops. Such a mechanism forms anautomatic control of the volume of liquid flows into the test chamber.

The devices of the invention can be used, for example, for testing bodyfluid samples, environmental samples, stool, and other samples.Substances can be tested using the devices of the invention includedrugs of abuse, therapeutic drugs, infectious pathogens, antibodies,blood components, environmental pollutants, such as micro-organisms,explosives, and poisons. The devices of the invention are suitable fortesting specimens selected, for example, from the group consisting ofstool, blood, urine, and saliva, microbe culture media, and swabspecimens of surfaces of an animal, such as the cervix, urethra,nostril, and throat, as well as environmental specimens, such as foodproducts, soil and dust samples. By animal is meant, for example, anylive or dead animal including, for example, a mammal, for example, ahuman. Substances to be tested in these specimens include but are notlimited to fecal occult blood components, hapto-hemoglobin complex,antibodies, bacteria, viruses, enzymes, proteins, drugs, substances ofabuse, allergens, pesticides, and pollutants.

The reagent member can be in liquid, or dry form. In one embodiment ofthe invention, the reagent member of the test device is a liquidsolution comprising reagents capable of reacting with analytes of thesample solution to be tested and produce an assay signal indicative ofthe presence or quantity of at least one analytes of the samplesolution. In another embodiment of the invention, the assay reagent is adry reagent comprising reagents capable of reacting with analytes of thesample solution to be tested and produce an assay signal indicative ofthe presence or quantity of at least one analytes of the samplesolution. Dry reagents, air-dried or lyophilized, have longer shelf lifethan liquid reagents. A preferred dry form of assay reagent is, forexample, but not limited to, a dry reagent pad, a porous matrixcontaining the dry assay reagent. Such dry reagents are used for avariety of testing products, such as urine glucose, pH, creatinine, andalcohol test. Another example of a preferred dry reagent member is alateral flow test strip. Where the reagent member is a dry reagent, forexample, a test strip, it is understood by those in the art that thetest assembly may comprise more than 1 reagent member, for example, eachreagent member comprising reagents for a different analyze detectionassay. For example, a device for fecal occult blood test may comprise areagent member for detecting hemoglobin and another reagent member fordetecting hapto-hemoglobin complex.

The present invention also provides kits for detecting test substancesin solid, semi-solid, or liquid specimens. For example, provided arekits that comprise a device of he present invention. The kits mayfurther comprise instructions for testing for the presence of asubstance in a specimen, and may further comprise instructions forobtaining specimen samples. The kits may further comprise referencesamples that may be used to compare test results with the specimensamples.

Example 1 Test Chamber Device for Fecal Occult Blood Test

A fecal occult blood test is an immunoassay based test method fordetection of blood in stool specimens. The presence of hemoglobin infeces can be indicative of gastrointestinal tract conditions associatedwith bleeding such as, for example, colorectal carcinoma, colon polyps,Crohn's disease, and ulcerative colitis. The present example provides a2-in-1 sample preparation and test device, that does not require liquidpipetting or transfer of the sample or sample solution. A fecal sampleis collected and prepared for testing using the fecal collection probe,or sample stick, attached to the cap of the test assembly of theinvention. The collection probe is inserted into a fecal specimen atseveral different sites. Excess sample is removed from the stick bygentle wiping with an absorbent tissue. The probe is reinserted into thetube and the cap is tightened securely. The tube is shaken vigorously toobtain a liquid suspension of the sample. Holding the tube upright, thebottom part of the chamber assembly is loosened about 1 revolution(360°). This allows the sample solution inside of the sample receivingchamber to flow into the test chamber. The device is kept in an uprightposition for 5 minutes, after which time the results may be read.Waiting for more than 10 minutes may cause the reading to be inaccurate.A negative test is indicated when one rose-pink color band appears inthe control zone, meaning that the fecal sample does not contain adetectable level of human hemoglobin. A positive test is indicated whentwo rose-pink color bands appear, one in the test (T) zone and one inthe control (c) zone, A positive result indicates that the specimencontains human hemoglobin. An invalid test is indicated where after fiveminutes, no bands appear, or a test band appears without a control bandappearing.

The entirety of each patent, patent application, publication anddocument referenced herein hereby is incorporated by reference. Citationof the above patents, latent applications, publications and documents isnot an admission that any of the foregoing is pertinent prior art, nordoes it constitute any admission as to the contents or date of thesepublications or documents.

Singular forms “a”, “an”, and “the” include plural reference unless thecontext clearly dictates otherwise. Thus, for example, reference to “asubset” includes a plurality of such subsets. Reference to “a nucleicacid” includes one or more nucleic acids and equivalents thereof knownto those skilled in the art, and so forth. The term “or” is not meant tobe exclusive to one or the terms it designates. For example, as it isused in a phrase of the structure “A or B” may denote A alone, B alone,or both A and B.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art to which this invention belongs. Although any methods andsystems similar or equivalent to those described herein can be used inthe practice or testing of the present invention, the methods, devices,and materials are now described. All publications mentioned herein areincorporated herein by reference for the purpose of describing anddisclosing the processes, systems, and methodologies which are reportedin the publications which might be used in connection with theinvention. Nothing herein is to be construed as an admission that theinvention is not entitled to antedate such disclosure by virtue of priorinvention.

Modifications may be made to the foregoing without departing from thebasic aspects of the invention. Although the invention has beendescribed in substantial detail with reference to one or more specificembodiments, those of ordinary skill in the art will recognize thatchanges may be made to the embodiments specifically disclosed in thisapplication, and yet these modifications and improvements are within thescope and spirit of the invention. The invention illustrativelydescribed herein suitably may be practiced in the absence of anyelement(s) not specifically disclosed herein. Thus, for example, in eachinstance herein any of the terms “comprising”, “consisting essentiallyof”, and “consisting of may be replaced with either of the other twoterms. Thus, the terms and expressions which have been employed are usedas terms of description and not of limitation, equivalents of thefeatures shown and described, or portions thereof, are not excluded, andit is recognized that various modifications are possible within thescope of the invention. Embodiments of the invention are set forth inthe following claims.

1. A device for testing a specimen, comprising: (a) a test assemblycomprising (i) a sample receiving chamber; (ii) a test chamber; (iii) aseptum wall separating the sample receiving chamber and the testchamber; (iv) an opening in the septum wall so that the sample receivingchamber and the test area are in fluid communication; (v) a reagentmember positioned in the test chamber, the reagent member having a wickon and a test area comprising at least one assay reagent; (vi) abreakable seal for preventing flow of the sample from the samplereceiving chamber to the test chamber; and (viii) means for breaking theseal and allowing the sample to flow from the sample receiving chamberto the test chamber.
 2. The device of claim 1, where the samplereceiving chamber includes a test buffer.
 3. The device of claim 1,where the means for breaking the seal is attached to a lower end of thele receiving chamber.
 4. The device of claim 1, where the test assemblyis formed of a plastic selected from the group sting of polyethylene,polypropylene, polystyrene polyvinyl, and acrylonitrile butadienestyrene.
 5. The device of claim 1, further comprising: (b) a capincluding a handle and an insert section sized to fit within an upperend of the test assembly.
 6. The device of claim 1, where the reagentmember is a lateral flow test strip.
 7. The device of claim 1,comprising at least two reagent members.
 8. The device of claim 1,comprising from 3-5 reagent members.
 9. The device of claim 1, where theassay reagent detects hemoglobin.
 10. The device of claim 1, where theassay reagent detects a hapto-hemoglobin complex.
 11. A method of usingthe device of claim 1, comprising: introducing a sample solution intothe sample receiving chamber; mixing the sample with a buffer in thesample receiving chamber; breaking the seal; introducing the sample intothe test chamber through the opening; and reacting the sample with theassay reagent of the reagent member.
 12. The method of claim 11, wheresaid device further includes a cap including a handle and an t sized tofit within an upper end of the test assembly, the method furthercomprising: lowering the handle such that the insert section is insertedinto the test assembly to move the means for breaking the seal to breakthe seal.